Dermal wound healing involves several phases: hemostasis, inflammation, proliferation, and tissue maturation. The overall process is induced and regulated by a complex array of factors, such as growth factors and cytokines.
The initial hemostasis controls the release of a variety of growth factors and/or cytokines from activated platelets to promote blood clotting. The hemostasis phase is followed by the inflammation phase.
The inflammation phase induces vasodilation and results in an influx of lymphocytes and macrophages. Macrophages will release growth factors, such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-1 (IL-1), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF) that stimulate fibroblasts cells to promote the proliferation phase.
As the proliferative phase progresses, these growth factors stimulate angiogenesis and fibroplasias to rebuild blood flow to tissues after injury. Finally, the tissues mature to complete the wound healing processes. The tissue maturation phase also requires growth factors to control cell differentiation.
Because the wound healing processes involve multiple phases that require different factors at different times, any improper action of these factors in any phase may result in improper wound healing. For example, excessive fibrosis may lead to undesirable scar formation.
Given these multiple factors and their spatial and temporal interactions, identifying an appropriate drug treatment strategy is challenging. For effective controls of dermal wound healing, a therapy may need to modulate more than one phase and target for a positive wound repair outcome.